Pyrrolo[2,3-d]pyrimidine compounds are potent inhibitors of protein kinases such as the enzyme Janus Kinase 3 (JAK 3) and are therefore useful for the treatment of a wide variety of immunological disorders. Such disorders include but are not limited to lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type 1 diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease and leukemia. The compounds are also useful in the treatment and prevention of chronic or acute organ transplant rejection (allografts and xenograft).
Specific pyrrolo[2,3-d]pyrimidine compounds, their methods of use, and their synthesis and intermediates have previously been described in U.S. Pat. No. 6,627,754, WO 02096909, WO 03048162 and US published application 2004/0102627A1 commonly assigned to the assignee of the present invention, all of which are incorporated by reference in their entirety. U.S. Pat. No. 6,627,754 describes the compound 3-{4-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino}-piperidin-1-yl)-3-oxo-propionitrile and its corresponding citrate salt as useful inhibitors of protein kinases (such as the enzyme JAK 3) and as such are useful for therapy as immunosuppressive agents for organ transplants, xeno transplantation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type 1 diabetes and complication from diabetes, cancer, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukemia and other indications where immune suppression would be desirable. US published application 2004/0102627A1 describes the synthesis of an intermediate, cis-(1-benzyl-4-methyl-piperidin-3-yl)-methyl-amine hydrochloride salt, which is useful in the synthesis of 3-{(3R,4R)-4-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino}-piperidin-1-yl)-3-oxo-propionitrile and its corresponding citrate salt.